Phase II study of fenretinide in patients with small cell lung cancer (SCLC) with progression after first- or second-line chemotherapy. B. J. Schneider, F. Worden, S. Gadgeel, C. Hodges, R. Parchment, J. Zwiebel, M. Kraut, G. Kalemkerian; University of Michigan, Ann Arbor, MI; Wayne State University, Detroit, MI; National Cancer Institute, Rockville, MD Abstract: Background: Alterations in retinoid signaling appear to be involved in the pathogenesis of SCLC. Fenretinide [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid, inhibits the growth of SCLC cells in vitro via the induction of apoptosis. We evaluated the clinical activity of fenretinide in relapsed/refractory SCLC. Methods: Inclusion criteria included progressive SCLC after 1 or 2 chemotherapy regimens and PS 0-2. Patients with stable, treated CNS metastases were eligible. Fenretinide 900 mg/m² PO BID was administered on days 1-7 of each 21-day cycle. Blood and sputum were collected pre-treatment and on day 7 of cycle 1 to measure drug levels by HPLC. Results: 19 patients were enrolled: median age 63 yrs (43-80); gender 9M:10F; prior chemotherapy regimens 1 in 15 pts, 2 in 4 pts; median time from diagnosis to enrollment 10 months (7-40). The median number of cycles of fenretinide was 2 (1-17). Six of 18 evaluable patients (30%) had stable disease (SD) after 2-17 cycles. Eleven patients had progressive disease after 1 or 2 cycles, 2 of whom had progression of symptoms despite radiographic SD. The median time to treatment failure was 5.1 wk (1-19) in all patients and 13 wk in patients with SD. Median survival was 25 wk (6-125), with 3 patients alive at 40-70 wks. Toxicity included mild, reversible visual changes (haziness, altered night vision), grade 1-3 nausea/vomiting, and grade 1 diarrhea. One patient developed pancreatitis on day 2 of cycle 1 due to metastatic pancreatic duct obstruction. The average day 7 plasma fenretinide level was 3103 ± 1707 ng/ml (7.9 ± 4.4 µM; n=14). Average pre-treatment and day 7 serum retinol levels were 471 ± 159 ng/ml and 51 ± 71 ng/ml, respectively. Conclusions: Fenretinide is well tolerated in patients with SCLC. Concentrations of fenretinide that induce cytotoxicity in vitro are clinically achievable. Stabilization of disease has been noted in 30% of patients with this aggressive disease. Abstract No: 7299 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.